Intracranial activity of lapatinib has been demonstrated in several studies in patients with human epidermal growth factor receptor-2 positive breast cancers (HER-2+ BC). Stereotactic radiosurgery (SRS) has been increasingly used as the local therapy for brain metastases in breast cancer patients. Increased objective response rate was observed for lapatinib plus whole brain radiotherapy (WBRT) is such patients with high toxicity.
We seek to obtain clinical evidence of synergistic efficacy of lapatinib in combination with radiation therapy, in particular, SRS.
We carried out a comprehensive research using the following databases PubMed; Medline; EMBASE; Cochrane library. These databases were searched until 10 June 2020. PRISMA guidelines were followed step by step for carrying out this systematic review and meta-analysis. Review Manager v 5.4 software was used for statistical evaluation of data.
Overall 6 studies with 843 HER-2 positive breast cancer patients (442 HER-2 amplified disease, 399 luminal B001) and lower progressive disease rate of 11 vs. 19% (p &lt; 0.001). Risk of radiation necrosis was decreased with lapatinib use.
Lapatinib has shown intracranial activity and yielded better survival for HER-2+ BC patients with BMs. SRS in combination with ever use of lapatinib had better local control and were associated with better survival. Radiation necrosis risk was reduced with the use of lapatinib.
Lapatinib has shown intracranial activity and yielded better survival for HER-2+ BC patients with BMs. SRS in combination with ever use of lapatinib had better local control and were associated with better survival. Radiation necrosis risk was reduced with the use of lapatinib.Tumor mutation burden (TMB) and tumor infiltrating lymphocytes have been well-recognized as molecular determinants of immunotherapeutic responsiveness in many types of cancer. However, the relationship between TMB with immune infiltrates and their prognostic role are reported occasionally in skin cutaneous melanoma (SKCM). We obtained the somatic mutation data and transcriptome profiles of 454 SKCM patients from The Cancer Genome Atlas (TCGA) database, and analyzed the mutation profiles using "maftools" package. Correlation analysis revealed that lower TMB levels conferred poor survival outcomes, associated with lower age and advanced pathological stage. Differential analysis was conducted to the genome expression between two TMB groups using "limma" package, and we identified four hub TMB-related immune genes including CNTFR, CRABP2, GAL, and PAEP. We further analyzed the underlying relationships of the copy number variations (CNVs) of four hub genes with immune infiltrates in SKCM microenvironment through TIMER database. The results indicated that diverse forms of CNVs carried by hub genes could commonly inhibit immune infiltrates. Based on the CIBERSORT method, we compared the proportions of 22 immune cells in two TMB groups and assessed their prognostic value. The data revealed that infiltrations levels of regulatory T (Treg) cell and dendritic activated cells in high-TMB group were lower than that in low-TMB group, while M1 and M2 macrophages showed the opposite trend, especially the levels of neutrophil and macrophage correlated positively with prognosis of SKCM. Finally, we constructed a TMB Prognostic Index (TMBPI) to evaluate the predictive accuracy of the four hub TMB-related immune genes. https://www.selleckchem.com/peptide/angiotensin-ii-human-acetate.html The ROC curve was drawn to assess the predictive accuracy with AUC = 0.664 and higher TMBPI conferred poor survival outcomes, which warranted further investigation and larger samples to validate.The immune system is able to recognize and eliminate tumor cells. Some tumors, including colorectal cancer (CRC), induce immune tolerance via different mechanisms of "immunoediting" and "immune evasion" and can thus escape immune surveillance. The impact of immunotherapy on cancer has been investigated for many years, but so far, the application was limited to few cancer types. Immuno-oncological therapeutic strategies against metastatic colorectal cancer (mCRC), the adaptive immune system activating approaches, offer a high potential for adaptation to the great heterogeneity of CRC. Moreover, novel treatment approaches are currently being tested that might specifically target the disease initiating and maintaining population of colorectal cancer stem cells (CSCs). In this review, we aim to summarize the current state of immune-oncology and tumor immunotherapy of patients with mCRC and discuss different therapeutic modalities that focus on the activation of tumor-specific T-cells and their perspectives such as tumor vaccination, checkpoint inhibition, and adoptive T-cell transfer or on the eradication of colorectal CSCs.Adjuvant radiotherapy is the main treatment modality for high grade meningioma after surgical resection; however, recurrence and survival outcomes vary. The aim of this study was to create a new "prognostic score" that allows personalized recommendations for post-operative adjuvant radiotherapy in patients with high grade meningioma.
Clinical data were collected from 115 patients with high grade meningioma treated with surgical resection and adjuvant radiotherapy. A prognostic model was built based on the hazards ratios of independent prognostic factors yielded by multivariate cox proportional analysis. Calibration and discrimination of the prognostic score was evaluated using good of fit test and Harrel's C index, respectively.
A total of 115 high grade meningioma patients (72 atypical and 43 anaplastic meningiomas) were enrolled. Three factors were independently associated with progression-free survival (PFS) extent of resection (GTR vs. STR), recurrent status (vs. recurrent), and Ki-67 labeling index (&lt;5% vs. ? 5%). The respective β-coefficients were used to generate the "prognostic score". The cohort was divided into low-risk and high-risk groups based on the median prognostic score. Good of fit test showed strong calibration (P = 0.7133) and Harrel's C index 0.766 indicated a strong discrimination capability of the prognostic score. The Harrel's C index for OS was 0.60.
Our prognostic model using three basic clinical parameters robustly separated high grade meningioma patients who benefit vs. do not benefit from adjuvant radiotherapy. External validation of our model is warranted to help improve patient selection suitable for adjuvant radiotherapy.
Our prognostic model using three basic clinical parameters robustly separated high grade meningioma patients who benefit vs. do not benefit from adjuvant radiotherapy. External validation of our model is warranted to help improve patient selection suitable for adjuvant radiotherapy.